Mechanical forces directing intestinal form and function

Houtekamer, Ronja M.; Net, Mirjam C. van der; Maurice, Madelon M.; Gloerich, Martijn

doi:10.1016/j.cub.2022.05.041

Cited by 16 publications

(9 citation statements)

References 133 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…During intestinal organoid development, local changes in epithelial cell shape are necessary to drive symmetry breaking events that lead to crypt formation, but there is little understanding of the role of epithelial curvature induced mechanotransduction in directing crypt development ( 35 ). Specifically, we were interested in understanding how mechanotransduction pathways are temporally regulated to influence symmetry breaking events.…”

Section: Discussionmentioning

confidence: 99%

In situ modulation of intestinal organoid epithelial curvature through photoinduced viscoelasticity directs crypt morphogenesis

et al. 2023

View full text Add to dashboard Cite

Spatiotemporally coordinated transformations in epithelial curvature are necessary to generate crypt-villus structures during intestinal development. However, the temporal regulation of mechanotransduction pathways that drive crypt morphogenesis remains understudied. Intestinal organoids have proven useful to study crypt morphogenesis in vitro, yet the reliance on static culture scaffolds limits the ability to assess the temporal effects of changing curvature. Here, a photoinduced hydrogel cross-link exchange reaction is used to spatiotemporally alter epithelial curvature and study how dynamic changes in curvature influence mechanotransduction pathways to instruct crypt morphogenesis. Photopatterned curvature increased membrane tension and depolarization, which was required for subsequent nuclear localization of yes-associated protein 1 (YAP) observed 24 hours following curvature change. Curvature-directed crypt morphogenesis only occurred following a delay in the induction of differentiation that coincided with the delay in spatially restricted YAP localization, indicating that dynamic changes in curvature initiate epithelial curvature–dependent mechanotransduction pathways that temporally regulate crypt morphogenesis.

show abstract

Section: Discussionmentioning

confidence: 99%

In situ modulation of intestinal organoid epithelial curvature through photoinduced viscoelasticity directs crypt morphogenesis

et al. 2023

View full text Add to dashboard Cite

show abstract

“…In ICS ( Houtekamer et al, 2022 ), β1-integrins have been identified as important regulators of proliferation and homeostasis by mediating Hedgehog signaling in a genetic study in mice ( Jones et al, 2006 ). Additionally, β1-integrins via an integrin-linked kinase (ILK) -fibronectin-dependent mechanism regulate ISCs fate ( Gagné et al, 2010 ).…”

Section: Mechanosignaling In the Three Epitheliamentioning

confidence: 99%

ECM and epithelial stem cells: the scaffold of destiny

Estrach,

Vivier,

Féral

2024

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Adult stem cells play a critical role in maintaining tissue homeostasis and promoting longevity. The intricate organization and presence of common markers among adult epithelial stem cells in the intestine, lung, and skin serve as hallmarks of these cells. The specific location pattern of these cells within their respective organs highlights the significance of the niche in which they reside. The extracellular matrix (ECM) not only provides physical support but also acts as a reservoir for various biochemical and biophysical signals. We will consider differences in proliferation, repair, and regenerative capacities of the three epithelia and review how environmental cues emerging from the niche regulate cell fate. These cues are transduced via mechanosignaling, regulating gene expression, and bring us to the concept of the fate scaffold. Understanding both the analogies and discrepancies in the mechanisms that govern stem cell fate in various organs can offer valuable insights for rejuvenation therapy and tissue engineering.

show abstract

“…Cell collective mechanics are the proximate cause of tissue morphogenesis (1) -the tissue growth, shape change, and compartment interfacial geometry that determine normal and diseased organ function (Fig 1A). Interactions between cell tension, adhesion, proliferation, and migration sculpt many organs and feed back on cell behavior, for example in heart tube looping, craniofacial development, and condensation of hair follicle, feather, gut villus, and limb bud/digit structures (2)(3)(4)(5)(6)(7)(8). The formation of blood-filtering nephron structures in the developing kidney is an archetypal example of the relationship between radical mechanical and morphological transitions (9,10).…”

Section: Introductionmentioning

confidence: 99%

“…For example, ureteric bud aggregates (22) surrounded by SIX2+ nephron progenitors capable of rudimentary bona fide branching (46) and some connectivity with distal domains of nearby re-forming nephrons (47,48). Researchers have made significant progress in defining a 'cadherin code' that distinguishes anatomical compartments, namely differential expression of cadherins between naive nephron progenitors (Cdh2, 4,6) and those undergoing MET to renal vesicles and later stages associated with nephron segmentation (Cdh1, 2, 3,4,6,11,16) (22,23,25,49,50). However, cadherin expression alone is not necessarily predictive of self-organization outcomes (51).…”

Section: Introductionmentioning

confidence: 99%

Measurement of adhesion and traction of cells at high yield (MATCHY) reveals an energetic ratchet driving nephron condensation

Liu,

Prahl,

Huang

et al. 2024

Preprint

View full text Add to dashboard Cite

Engineering of embryonic strategies for tissue-building has extraordinary promise for regenerative medicine. This has led to a resurgence in interest in the relationship between cell biophysical properties and morphological transitions. However, mapping gene or protein expression data to cell biophysical properties to physical morphogenesis remains challenging with current techniques. Here we present MATCHY (multiplexed adhesion and traction of cells at high yield). MATCHY advances the multiplexing and throughput capabilities of existing traction force and cell-cell adhesion assays using microfabrication and an automated computation scheme with machine learning-driven cell segmentation. Both biophysical assays are coupled with serial downstream immunofluorescence to extract cell type/signaling state information. MATCHY is especially suited to complex primary tissue-, organoid-, or biopsy-derived cell mixtures since it does not rely on a priori knowledge of cell surface markers, cell sorting, or use of lineage-specific reporter animals. We first validate MATCHY on canine kidney epithelial cells engineered for RET tyrosine kinase expression and quantify a relationship between downstream signaling and cell traction. We go on to create a biophysical atlas of primary cells dissociated from the mouse embryonic kidney and use MATCHY to identify distinct biophysical states along the nephron differentiation trajectory. Our data complement expression-level knowledge of adhesion molecule changes that accompany nephron differentiation with quantitative biophysical information. These data reveal an 'energetic ratchet' that explains spatial nephron progenitor cell condensation from the niche as they differentiate, which we validate through agent-based computational simulation. MATCHY offers automated cell biophysical characterization at >10,000-cell throughput, a highly enabling advance for fundamental studies and new synthetic tissue design strategies for regenerative medicine.

show abstract

Mechanical forces directing intestinal form and function

Cited by 16 publications

References 133 publications

In situ modulation of intestinal organoid epithelial curvature through photoinduced viscoelasticity directs crypt morphogenesis

In situ modulation of intestinal organoid epithelial curvature through photoinduced viscoelasticity directs crypt morphogenesis

ECM and epithelial stem cells: the scaffold of destiny

Measurement of adhesion and traction of cells at high yield (MATCHY) reveals an energetic ratchet driving nephron condensation

Contact Info

Product

Resources

About